Electrode for making in vivo ionic measurements of venous blood



United States Patent Hideo Watanabe [72] Inventors Fullerton,California; Robert D. Gafford, Santa Ana, California [21] Appl. No.453,281 [22] Filed May 5, 1965 [45] Patented Sept. 29, 1970 [73]Assignee Beckman Instruments, Inc. a corporation of California [54]ELECTRODE FOR MAKING IN VIVO IONIC MEASUREMENTS OF VENOUS BLOOD 5Claims, 2 Drawing Figs.

[52] U.S. C1 128/2, 204/ I 95 [51] Int. Cl A61b 5/00 [50] FieldofSearch.... 128/2.l,2; 20411.1, 195.1, 195; 128]].05

[56] References Cited UNITED STATES PATENTS 2,168,867 8/1939 George204/195X 3,244,607 4/1966 Leonard et al.... 204/ l 95 3,334,623 8/1967Hillier etal. 128/2.05

Adler: fScientific Apparatus, in Science for Oct. 25, 1940, pages 385,386. Primary Examiner Dalton L. Truluck Attorneys-Thomas L. Peterson andRobert .1. Steinmeyer ABSTRACT: A miniature electrode for making in vivoionic measurements of venous blood in which the ion measuring electrodeis positioned entirely in front of the reference electrode to minimizethe cross sectional area of the assembly. The reference electrodeincludes a flexible catheter tube which holds the electrolyte of thereference electrode. The catheter tube may be filled with a sufficientquantity of electrolyte to expand the tube whereby the tube exerts apositive pressure on the electrolyte therein and thereby produces aconstant flow of electrolyte through the liquid junction of thereference electrode regardless of the position of the assembly.

Patented Sept. 29, 1970 30,849

I INVENTORS HIDEO WATANABE FIG. 2 ROBERT D. GAFFORD ATTORNEY ELECTRODEFOR'MAKING IN VIVO IONIC MEASUREMENTS OF VENOUS. BLOOD.

This invention relates to an electrochemical electrode assembly formeasuring the ionic concentration of a sample medium and, in particular,to an electrochemical electrode assembly for making in vivo pHmeasurements of venous blood or tissues of, human or animal subjects.

Current medical research indicates that low tissue and venous blood pHin human or animal subjects may be used as an indicator-for primaryhemorrhagic shock. Furthermore, it is believed that correction of thelow pH of venous blood and vital organs by means of intravenousinjection of adequate quantities of sterile bicarbonate buffer mayimprove the prognosis for a subjectin shock In other words, if thetissue acidosis resulting from ischemia can be neutralized, the subjectwill be better able to survive and re-establish adequate circulation.

At the present time there is no instrument available which is capable ofmaking in vivo pH measurements in the venous luminaof major internalorgans to permit the diagnosis and treatment described above. It is theconventional practice today to measure the pH of venous blood bywithdrawing blood from a vein by a syringe and delivering the blood to aflow cell having pH electrodes mounted therein. This method has thedisadvantage, however, that the pH of the blood may not be measuredcompletely anaerobically, that is, without exposure to air, thuspossiblyresulting in some errors in the pH measurement. Also, it isnecessary that the flow cell in which the blood sample is measured haveclose temperature control to simulate the temperature of thesubjectbeing diagnosed. Any difference in the temperature of the bloodbeing measured in the flow cell and that inside the body might alsoproduce a source of error. Furthermore, by the present method only thepH of blood withdrawn from peripheral veins maybe measured which may bedifferent than the pH of blood at points inside the body in the venouslumina of certain major internal organs.

Therefore, what is needed is an instrument for making in vivo pHmeasurements of venous blood in deep tissue or near major internalorgans. The instrument should be capable of being positioned in theveins of a patient or experimental subject with a minimum of surgicaltrauma. Also, it must be capable of making the required measurement withaccuracy and precision; preferably the accuracy should be better than .1pH unit as a minimum. in addition, the instrument should establish astable, well-coupled reference point and preclude interference from theelectrical activity of the heart or other muscles and nervous tissue andfrom the electrical impedance differences from various points of thebody. This requires that the reference electrode for the pH measuringinstrument be positioned very close to the pH electrode, yet theassembly must be sufficiently small to permit it to be readily insertedthrough the veinsof the subject being examined. Also, a stablepressurized reference junction should be provided for the referenceelectrode ofthe instrument.

It is an object of the present invention to provide an electrochcmiealelectrodeassembly for making in vivo ionic measurements of venous bloodor tissures of human or animal subjects having the above desiredcharacteristics.

According to a principal aspect of the present invention, there isprovided a miniaturized combination ion measuring reference electrodeassembly in which the ion measuring electrodeportion of the assembly issealed to one end of the reference electrode portion of the assemblythus permitting the assembly to have a substantially smaller crosssection than that of conventional combination measuring-referenceelectrodes.1Hence,:the assembly may be made sufficiently small to bemounted in an elongated flexible tube of very small diameter,'generallyreferred to as a catheter. which can be positioned in a vein or othersmall organ ofa human or animal subject for making in vivo ionicmeasurements. Also, the catheter forms a part of the reference electrodein that it provides a salt bridge spacewhcreby a sufficient supplyofsalt bridge solution is available to maintain ionic communicationbetween the intemal half cell of the reference electrode and the samplemedium for a substantial period of time.

According to another aspect of the invention, the salt bridge spaceprovided by the catheter in the above-described assembly is filled witha sufficient quantity of salt bridge solution so as to expand theelastic wall of the catheter. The expanded catheter exerts a positivepressure on the salt bridge solution thereby providing apressurizedreference junction for the assembly. Consequently, by thisfeature the assembly may be disposed at any position and salt solutionwill still flow through the liquid junction so long as the solutionremains pressurized by the expanded catheter. According to still anotheraspect of the invention, a fibrous material is positioned in the saltbridge space provided by the catheter so as to ensure continuouselectrolytic communication between the leak structure and the internalhalf cell of the reference electrode for a substantialtime even thoughbubbles might eventually form in the salt bridge space.

Other objects, aspects and advantages will become apparent from thefollowing description taken in connection with the accompanyingdrawingwherein:

FIG. 1 is a greatly enlarged cross sectional view of the forward portionof the electrochemical electrode assembly of the invention; and

H6. 2 is an enlarged partial cross sectional view of the rear portion ofthe assemblyincluding the connectors for connection to, anexternal'electrical circuit, not shown.

Referring now to the drawing in detail, there is illustrated theelectrochemical electrode assembly of the present invention whichcomprises generally an ion measuring electrode 10 and a referenceelectrode 12 having as a portion thereof an elongated flexible tube orcatheter 14 formed of an elastic nonconductive material such as siliconerubber. The ion measuring electrode 10 and the reference electrode 12together with the catheter 14 are sufficiently small in cross section topermit the insertion of the entire assembly into the veins of animal orhuman subjects, which requires that the outside diameter of the assemblybe no more than about 3 millimeters. The assembly also must be ofsufficient length to permit the insertion of the assembly in the vein ofan animal or a human subject so that the sensing portion of the ionmeasuring electrode 10 will reach the heart or other internal organswhere the in vivo ionic measurement of blood or tissues is required.

The ion measuring electrode 10 comprises a tubular member ofnonconductive material 16, preferably a conventional stem glass forglass electrodes, and an ion sensitive barrier l8 closes the forward endof the tubular member 16. The ion sensitive barrier may be formed of anymaterial which is sensitive to the ions thatare desired to be measuredand may take the form of a bulb, as illustrated, or a flat barrier ifdesired. In the preferred embodiment of the present invention,

the barrier 18 is formed of pH sensitive glass formed in theconfiguration of a bulb which is sealed by fusion to the end of thetubular member 16.

A conductor 20 is positioned in the tubular member 16 and extendsthrough the rear open end of the tubular member and through the entirereference electrode assembly 12 including the catheter 14 for connectionto a cable 22 having a connector 24 at the endthereof for connection toa suitable external circuit, such as a conventional pH meter (notshown). The conductor 20 is coated with a nonconductive material such asrubber to form an insulating sleeve 26 along its entire length exceptfor the portion in the glass tubular member 16 which is connected to ahalf cell 28 immersed in a suitable electrolyte solution 30. Preferably,the conductor 20 is a silver wire and the half cell 28 comprises acoatingof silver-chloride formed on the endof the silver wire 20. Therear portion of the tubu-, lar member 16 is sealed off from theremainder of the electrode assembly by cementing the insulating sleeve26 into the rear portion of the tubular member by silicone cement orother suitable insulating cement 32.

The reference electrode 12 of the assembly includes a glass tubularmember or sleeve 34, which may be formed also of other nonconductivematerials such as ceramic. The sleeve 34 surrounds the insulatingconductor 20 and is cemented at its forward end to the insulating sleeve26 of the conductor. Also, as seen in H6. 1, the forward portion of thesleeve 34 is cemented to the rear end of the glass tube 16 by the cement32. To ensure that the tube 16 and sleeve 34 are durably securedtogether, a rubber sleeve 36 surrounds a substantial part of the tube 16and a forward reduced portion of the sleeve 34 and is cemented thereto.Also, a suitable clamp 38 shown as a wire wound about the rubber sleeve36 over the forward portion of the sleeve 34 mechanically fixes the ionmeasuring electrode to the reference electrode assembly 12. Analternative to the rubber sleeve 36 and clamp 38 would be a sleeve ofheat shrinkable plastic which could be slipped over the tube 16 andsleeve 34 and, upon application of heat, would permanently conform tothe irregular shapes of the tube and sleeve, thus firmly securing thetwo parts together. An additional clamp 40 similar to clamp 38 securesthe forward portion of the catheter 14 to the rear of the sleeve 34. Thecatheter 14 may take the form of any flexible nonconductive material,but preferably is formed of silicone rubber.

A cavity 42 is provided in the rear portion of the sleeve 34 to providea salt bridge space 44 and a liquid junction or leak structure 46 isprovided in the wall 48 of the sleeve 34 to provide electrolyticcommunication between the space 44 and the outside of the electrodeassembly. Preferably the leak structure 46 comprises a palladium wiresealed in an opening in the wall 48 as described in US. Pat. No.2,705,220. However, it is understood that other leak structures may beprovided as, for example, porous ceramic plugs or asbestos fibers sealedinto the wall 48. It is merely important that the leak structure providea sufficiently slow passage of salt bridge solution from the referenceelectrode outside the assembly so that the blood or internal organs ofthe subject being examined are not exposed to appreciable quantities ofreference electrolyte.

The wall of the catheter 14 is spaced from the insulated conductor toprovide additional salt bridge space 50 in communication with the space44. The spaces 44 and 50, when filled with a suitable salt bridgesolution such as saturated KC 1 provide electrolytic connection betweena half cell 52 at the rear of the catheter l4 and the sample mediumthrough the leak structure 46. Since the space 50 is of substantiallength, a sufficient supply of salt bridge solution for the referenceelectrode 12 is available to ensure continuous electrolyticcommunication through the leak structure 46 when the electrode assemblyof the invention is implanted in a subject for monitoring the pH ofvenous blood over a substantial period of time.

According to one of the important features of the invention a sheath 53of fibrous material such as braided cloth is disposed in the catheter 14to facilitate the filling of the space 50 with salt bridge solution and,most importantly, since the sheath is impregnated with the saltsolution, the half cell 52 remains in electrolytic communication withthe sample through the leak structure 46 even though bubbles form in thespace 50.

it is understood that the half cell 52 may be positioned any placewithin the salt bridge space 50 or even the space 44 in the sleeve 34,but it is preferred to mount the half cell at the rear of the catheter14 as shown in FIG. 2, particularly if it results in increasing thediameter of the assembly. However, the increased diameter of the end ofthe assembly would be of no consequence since it would be external ofthe subject being examined. The half cell 52 may comprise a silver wire54 coated with silver chloride. The wire 54 is covered with aninsulation 56 and passes through a body 58 of fibrous material into thecable 22 and terminates in a lead 60 having a connector 62 forconnection into the reference electrode terminal of a pH meter, notshown. The cable 22 is fixed to the rear of the catheter 14 by a saltbridge filling assembly 64.

The filling assembly 64 comprises a tube 66 of nonconductive materialsurrounding the braided cloth body 58 and a ring 68 rotatably mounted onthe tube. The ring has an opening 70 therein which is adapted to bepositioned in alignment with an opening 72 in the tube 66 to permitdelivery of salt bridge solution into the space 50 as will be describedin detail later, The rear of the catheter 14 is secured to the forwardend of tube 66 by a suitable clamp 74, similar to clamp 38, while thesheath 76 of the cable 22 is secured to the rear of tube 66 by anotherclamp 78. An epoxy material 80 fills the rear portion of tube 66 andensures that the catheter is firmly connected to the cable 22.

It is seen from the above description and the drawing that the referenceelectrode 12 including the catheter 14 is mounted entirely behind therear portion of the ion measuring electrode 10, thereby producing acombination measuringreference electrode assembly having a sufficientlysmall cross section to permit its insertion into veins or other smallorgans. Also, by the construction of the assembly of the presentinvention, good insulation is provided between all electrical parts ofthe assembly, which is essential in ion measuring equipment, yet theassembly is still compact.

The space 50 of the catheter may be filled with salt solution byinserting the needle of a syringe containing the solution through theopenings 70 and 72, when aligned as shown in FIG. 2, and by forcing thesolution into the space. However, it is extremely difficult to fill thespace 50 in this manner without a considerable amount of bubbles formingin the space, which, of course, is undesirable. Therefore, it ispreferred to fill the space 50 with salt solution by immersing thefilling assembly end of the catheter 14 in a vessel of salt bridgesolution with the openings 70 and 72 aligned. Then an inverted bell jaris placed over the electrode assembly and the vessel and a vacuum isdrawn in the jar. This will cause the evacuation of the air in thecatheter 14 through the openings 70 and 72. Thereafter, the bell jar isremoved to break the vacuum so that atmospheric pressure forces the saltbridge solution in the vessel to completely fill the space 50 in thecatheter without the formation of any air bubbles in the space.

in order for the assembly to operate it is necessary that there beadequate flow of salt bridge solution through the leak structure 46 tothe sample media. This requires that a positive pressure be applied tothe salt bridge solution in the catheter. lf, when the electrodeassembly is used it is disposed so that a portion of the catheter 14 isabove the leak structure 46 then, due to the head of pressure of thesalt solution, a flow of the solution through the leak structure willresult. However, in

many cases the electrode assembly will be so disposed in the body beingexamined that there will be no positive pressure on the salt solution inthe vicinity of the leak structure 46. Therefore, according to anotherfeature of the invention, a slight positive pressure is applied to thesalt bridge solution regardless of the disposition of the electrodeassembly. This is achieved by taking advantage of the elastic nature ofthe catheter 14. After the salt bridge space 50 in the catheter has beenfilled with solution in the manner described above, an additional amountof solution is supplied under pressure to the space 50 via openings 70and 72 by a syringe. This will cause the catheter to expand toaccommodate the additional amount of solution. Thereafter the ring 68 isrotated to a position to close the opening 72. Since the expandedelastic catheter will tend to contract, a constant slight positivepressure is applied to the solution in space 50 thereby causing acontinuous flow of solution through the leak structure 46 so long assufficient solution remains in the catheter to keep it expanded.Generally, this pressurization of the solution by the catheter willcontinue for a sufficiently long period, due to the slow flow of thesolution through the leak structure 46, to meet most applications forthe electrode assembly of the invention. An electrochemical assembly hasbeen constructed in accordance with the invention having a length ofabout three feet and a diameter of approximately 3 millimeters. Thediameter of the ion sensitive barrier 18 was about 1.75 millimeterswhereas the leak structure 46 of the reference electrode was positionedapproximately 5 milliliters behind the ion sensitive barrier 18, whichis sufficiently close to the barrier to preclude interference fromelectrical activity from various points elsewhere in the body. Also,tests of the electrode assembly of the invention show that the impedanceof the assembly, its accuracy and reproducibility were well within therequired limits for satisfactory measurements of the pH of venous blood.

Although the present invention has been described as being ideallysuitable for measuring in vivo the pH of venous blood, the invention hasapplications for the same general use in any system where access may belimited, particularly through a tubular passage or where remote ionicmeasurements are desired.

Although only one embodiment of the invention has been disclosed hereinfor purposes of illustration, it will be understood that various changescan be made in the form, details, arrangement and proportions of thevarious parts in such embodiment without departing from the spirit andscope of the invention as defined by the appended claims.

We claim:

l. in an electrochemical electrode assembly for making in vivo ionicmeasurements of venous blood or the like, the combination of:

a reference electrode including an elongated elastic tube having a saltbridge space therein;

a liquid junction in said electrode adjacent to one end of said tube topermit ionic communication between said salt bridge space and theexterior of the electrode;

closure means closing the other end of said tube;

an internal half cell positioned in said salt bridge space;

a conductor connected to said half cell and extending through saidclosure means for connection to an external electrical circuit;

a wall of said closure means having an unoccluded passage extendingtherethrough to provide communication between said salt bridge space andthe exterior of said electrode;

said reference electrode being closed except for said liquid junctionand said passage; and

a valve element movably mounted on the outside of said wall between twopositions, in one position said valve element closing said passage andin the other position said valve element exposing said passage wherebyin said other position of said valve element salt bridge solution may beintroduced into said space under pressure to expand said elastic tubeand said solution may be maintained under pressure by shifting saidvalve element to said one position to close said passage and, further,whereby said expanded elastic tube will exert a positive pressure onsaid solution in said salt bridge space.

2. An electrochemical electrode assembly for making in vivo ionicmeasurements of venous blood or the like comprisreference electrodemeans including an elongated flexible tube of relatively small diameteradapted to be inserted into the veins or other organs of humans oranimal subjects;

ion measuring electrode means at one end of said reference electrodemeans and comprising a tubular member of nonconductive material havingan ion sensitive barrier closing one end of said member, a first halfcell in said tubular member for contacting an electrolyte solutiontherein. a first conductor connected to said half cell and extendingbeyond the other end of said tubular member and through said flexibletube for connection to an external circuit. and an insulating sleevesurrounding said first conductor and sealed to said other end of saidtubular member;

from said sleeve to define a first salt bridfge space, a leak structurein said wall at said other end 0 5a: second tubular member providingionic communication between said salt bridge space and the exterior ofsaid assembly;

said flexible tube having one end sealed to said other end of saidsecond tubular member and the wall of said flexible tube being spacedfrom said insulating sleeve to define a second salt bridge spacecommunicating with said first salt bridge space; and

a second half cell in one of said salt bridge spaces and a secondconductor connected to said second half cell and extending through saidother end of said flexible tube for connection to an external circuit.

3. An electrochemical electrode assembly as set forth in claim 2 whereinsaid first conductor is a silver wire and said first half cell comprisesa coating of silver chloride on said silver wire.

4. An electrochemical electrode assembly as set forth in claim 2including a sheath of fibrous material extending substantially thelength of said second salt bridge space in said elongated flexible tubefor facilitating the filling of said first and second salt bridge spaceswith salt bridge solution.

5. An electrochemical electrode assembly for making in vivo ionicmeasurements of venous blood or the like comprisreference electrodemeans including an elongated flexible tube having a sufficiently smallcross section to permit its insertion into the veins or other organs ofhuman or animal subjects;

ion measuring electrode means entirely at one end of said referenceelectrode means and comprising a tube of nonconductive glass having anion sensitive glass barrier closing one end thereof, electrolytesolution in said glass tube, a first half cell in said glass tubecontacting said electrolyte solution, a first conductor connected tosaid half cell and extending beyond the other end of said glass tube andthrough said flexible tube for connection to an external circuit, and aninsulating sleeve surrounding said first conductor and sealed in saidother end of said glass tube;

said reference electrode means also including a sleeve of nonconduetiveglass surrounding said insulating sleeve and having one end sealed tosaid sleeve and to said other end of said glass tube, the wall of saidglass sleeve at its other end being spaced from said insulating sleeveto define a first salt bridge space, a leak structure in said wall atsaid other end of said glass sleeve providing ionic communicationbetween said salt bridge space and the exterior of said assembly;

said flexible tube having one end sealed to said other end of said glasssleeve and the wall of said flexible tube being spaced from saidinsulating sleeve to define a second salt bridge space communicatingwith said first salt bridge space;

a second half cell in one of said salt bridge spaces and a secondconductor connected to said second half cell and extending through saidother end of said flexible tube for connection to an external circuit;and

a sheath of fibrous material extending substantially the length of saidsecond salt bridge space in said elongated flexible tube forfacilitating the filling of said first and second salt bridge spaceswith salt bridge solution.

